Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers.
Cancer Res Treat
; 51(1): 80-89, 2019 Jan.
Article
em En
| MEDLINE
| ID: mdl-29510614
ABSTRACT
PURPOSE:
In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cellâmediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. MATERIALS ANDMETHODS:
We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts.RESULTS:
In 668 consecutive breast cancer cohort, 40% of tumors showed high level of LMP7 expression, and tumors with high expression of LMP7 had more tumor-infiltrating lymphocytes (TILs) in each subtype of breast cancer. In another cohort of 681 triple-negative breast cancer patients cohort, the expression of LMP7 in tumor cells was significantly correlated with the amount of TILs and the expression of interferon-associated molecules (MxA [p < 0.001] and PKR [p < 0.001]), endoplasmic reticulum stress-associated molecules (PERK [p=0.012], p-eIF2a [p=0.001], and XBP1 [p < 0.001]), and damage-associated molecular patterns (HMGN1 [p < 0.001] and HMGB1 [p < 0.001]). Patients with higher LMP7 expression had better disease-free survival outcomes than those with no or low expression in the positive lymph node metastasis group (p=0.041).CONCLUSION:
Close association between the TIL levels and LMP7 expression in breast cancer indicates that better antigen presentation through greater LMP7 expression might be associated with more TILs.Palavras-chave
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Biomarcadores Tumorais
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Regulação para Cima
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Complexo de Endopeptidases do Proteassoma
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Cancer Res Treat
Ano de publicação:
2019
Tipo de documento:
Article